IZUMO1 is a sperm-specific single-pass type I membrane protein of the Izumo family, built from an N-terminal four-helix IZUMO domain, a beta-hairpin hinge and an immunoglobulin-like domain. It resides in the acrosomal membranes of the sperm head and becomes exposed on the sperm plasma membrane (equatorial segment) only after the acrosome reaction. There its ectodomain binds the GPI-anchored egg receptor JUNO (IZUMO1R) in a 1:1 complex, and in humans also engages the oolemmal receptor FCRL3/MAIA, providing the essential adhesion between gamete membranes that precedes sperm-egg fusion. IZUMO1 forms a conserved trimeric complex with SPACA6 and TMEM81 on sperm. Loss of Izumo1 in mice causes male sterility because sperm penetrate the zona pellucida but cannot fuse with the egg.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000768 syncytium formation by cell-cell fusion | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Orthology transfer of syncytium formation, based on the ability of mouse Izumo1 to drive fusion of cultured cells. Reason: IZUMO1 acts physiologically in gamete adhesion preceding sperm-egg fusion; the IZUMO1-JUNO interaction is an adhesion step and IZUMO1 is not established as the fusogen. A heterologous cell-fusion activity reported for mouse Izumo1 does not make the protein a participant in syncytium formation in vivo. Supporting Evidence: file:human/IZUMO1/IZUMO1-uniprot.txt The IZUMO1:IZUMO1R/JUNO interaction is a necessary adhesion event between sperm and egg that is required for fertilization but is not sufficient for cell fusion. |
| GO:0001669 acrosomal vesicle | ISS GO_REF:0000024 | MODIFY | Summary: IZUMO1 is in the acrosome of non-reacted sperm, specifically in its membranes. Reason: The parent compartment is correct, but the evidence places IZUMO1 as a type I membrane protein of the inner and outer acrosomal membranes; the more specific acrosomal membrane term, already carried by the gene, is preferred. Proposed replacements: acrosomal membrane Supporting Evidence: file:human/IZUMO1/IZUMO1-uniprot.txt Localizes initially to the acrosome membrane of the sperm head (both outer and inner acrosomal membranes) |
| GO:0002080 acrosomal membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IZUMO1 resides in the acrosomal membranes before the acrosome reaction. Reason: Human sperm immunolocalization places IZUMO1 in the acrosomal membranes before the acrosome reaction; this is the storage compartment from which it is exposed at the cell surface. Supporting Evidence: file:human/IZUMO1/IZUMO1-uniprot.txt Localizes initially to the acrosome membrane of the sperm head (both outer and inner acrosomal membranes) PMID:36070373 a soluble extracellular domain of FcRL3 protein bound to IZUMO1, which was relocated to the equatorial segment after the acrosome reaction |
| GO:0002080 acrosomal membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IZUMO1 resides in the acrosomal membranes before the acrosome reaction. Reason: Human sperm immunolocalization places IZUMO1 in the acrosomal membranes before the acrosome reaction; this is the storage compartment from which it is exposed at the cell surface. Supporting Evidence: file:human/IZUMO1/IZUMO1-uniprot.txt Localizes initially to the acrosome membrane of the sperm head (both outer and inner acrosomal membranes) PMID:36070373 a soluble extracellular domain of FcRL3 protein bound to IZUMO1, which was relocated to the equatorial segment after the acrosome reaction |
| GO:0002080 acrosomal membrane | ISS GO_REF:0000024 | ACCEPT | Summary: IZUMO1 resides in the acrosomal membranes before the acrosome reaction. Reason: Human sperm immunolocalization places IZUMO1 in the acrosomal membranes before the acrosome reaction; this is the storage compartment from which it is exposed at the cell surface. Supporting Evidence: file:human/IZUMO1/IZUMO1-uniprot.txt Localizes initially to the acrosome membrane of the sperm head (both outer and inner acrosomal membranes) PMID:36070373 a soluble extracellular domain of FcRL3 protein bound to IZUMO1, which was relocated to the equatorial segment after the acrosome reaction |
| GO:0005102 signaling receptor binding | IEA GO_REF:0000002 | MODIFY | Summary: IZUMO1 binds the egg membrane protein JUNO (IZUMO1R), which is annotated as its receptor. Reason: The JUNO interaction is direct and well established, including in humans, but JUNO is a GPI-anchored adhesion receptor with no demonstrated signaling output. The binding acts in heterotypic gamete adhesion, so the adhesion-specific binding term (already carried by the gene through IBA) describes the activity more accurately than signaling receptor binding. Proposed replacements: protein binding involved in heterotypic cell-cell adhesion Supporting Evidence: PMID:24739963 We show that the Izumo1-Juno interaction is conserved within several mammalian species, including humans. PMID:27309808 The central Ξ²-hairpin region of IZUMO1 provides the main platform for JUNO binding |
| GO:0005102 signaling receptor binding | IPI PMID:24739963 Juno is the egg Izumo receptor and is essential for mammalia... | MODIFY | Summary: IZUMO1 binds the egg membrane protein JUNO (IZUMO1R), which is annotated as its receptor. Reason: The JUNO interaction is direct and well established, including in humans, but JUNO is a GPI-anchored adhesion receptor with no demonstrated signaling output. The binding acts in heterotypic gamete adhesion, so the adhesion-specific binding term (already carried by the gene through IBA) describes the activity more accurately than signaling receptor binding. Proposed replacements: protein binding involved in heterotypic cell-cell adhesion Supporting Evidence: PMID:24739963 We show that the Izumo1-Juno interaction is conserved within several mammalian species, including humans. PMID:27309808 The central Ξ²-hairpin region of IZUMO1 provides the main platform for JUNO binding |
| GO:0005515 protein binding | IPI PMID:27309808 Structure of IZUMO1-JUNO reveals sperm-oocyte recognition du... | MODIFY | Summary: Structural and biophysical evidence for the human IZUMO1-JUNO complex. Reason: Following the protein-binding policy, the generic term is replaced by the informative activity the paper supports, binding of the egg receptor JUNO to mediate gamete adhesion. Proposed replacements: protein binding involved in heterotypic cell-cell adhesion Supporting Evidence: PMID:27309808 we show the crystal structures of human IZUMO1, JUNO and the IZUMO1-JUNO complex, establishing the structural basis for the IZUMO1-JUNO-mediated sperm-oocyte interaction |
| GO:0005789 endoplasmic reticulum membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse data indicate FREY-dependent retention of IZUMO1 in the ER of developing spermatids. Reason: The ER membrane is a biosynthetic/transit location during spermatogenesis where FREY coordinates IZUMO1 complex assembly; it is not the site of IZUMO1 function. Supporting Evidence: file:human/IZUMO1/IZUMO1-uniprot.txt Interacts with FREY; the interaction retains IZUMO1 at the endoplasmic reticulum membrane and coordinates IZUMO1 complex assembly |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: After the acrosome reaction IZUMO1 is exposed on the sperm plasma membrane with its ectodomain facing the egg. Reason: Sperm surface exposure after the acrosome reaction is where IZUMO1 binds JUNO and FCRL3/MAIA on the oolemma; antibody against human IZUMO1 blocks fusion of human sperm, consistent with an accessible extracellular domain. The plasma membrane is the functional location. Supporting Evidence: PMID:24739963 Izumo1 is an essential sperm cell-surface protein, but its receptor on the egg has not been described. PMID:15759005 Human sperm also contain Izumo and addition of the antibody against human Izumo left the sperm unable to fuse with zona-free hamster eggs. |
| GO:0005886 plasma membrane | IDA PMID:15759005 The immunoglobulin superfamily protein Izumo is required for... | ACCEPT | Summary: After the acrosome reaction IZUMO1 is exposed on the sperm plasma membrane with its ectodomain facing the egg. Reason: Sperm surface exposure after the acrosome reaction is where IZUMO1 binds JUNO and FCRL3/MAIA on the oolemma; antibody against human IZUMO1 blocks fusion of human sperm, consistent with an accessible extracellular domain. The plasma membrane is the functional location. The cell-type-restricted context (the sperm head plasma membrane, exposed only after the acrosome reaction) is carried by the sperm head plasma membrane (GO:1990913) core-function location rather than by a generic-term extension. Supporting Evidence: PMID:24739963 Izumo1 is an essential sperm cell-surface protein, but its receptor on the egg has not been described. PMID:15759005 Human sperm also contain Izumo and addition of the antibody against human Izumo left the sperm unable to fuse with zona-free hamster eggs. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: After the acrosome reaction IZUMO1 is exposed on the sperm plasma membrane with its ectodomain facing the egg. Reason: Sperm surface exposure after the acrosome reaction is where IZUMO1 binds JUNO and FCRL3/MAIA on the oolemma; antibody against human IZUMO1 blocks fusion of human sperm, consistent with an accessible extracellular domain. The plasma membrane is the functional location. Supporting Evidence: PMID:24739963 Izumo1 is an essential sperm cell-surface protein, but its receptor on the egg has not been described. PMID:15759005 Human sperm also contain Izumo and addition of the antibody against human Izumo left the sperm unable to fuse with zona-free hamster eggs. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: After the acrosome reaction IZUMO1 is exposed on the sperm plasma membrane with its ectodomain facing the egg. Reason: Sperm surface exposure after the acrosome reaction is where IZUMO1 binds JUNO and FCRL3/MAIA on the oolemma; antibody against human IZUMO1 blocks fusion of human sperm, consistent with an accessible extracellular domain. The plasma membrane is the functional location. Supporting Evidence: PMID:24739963 Izumo1 is an essential sperm cell-surface protein, but its receptor on the egg has not been described. PMID:15759005 Human sperm also contain Izumo and addition of the antibody against human Izumo left the sperm unable to fuse with zona-free hamster eggs. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1297275 | ACCEPT | Summary: After the acrosome reaction IZUMO1 is exposed on the sperm plasma membrane with its ectodomain facing the egg. Reason: Sperm surface exposure after the acrosome reaction is where IZUMO1 binds JUNO and FCRL3/MAIA on the oolemma; antibody against human IZUMO1 blocks fusion of human sperm, consistent with an accessible extracellular domain. The plasma membrane is the functional location. Supporting Evidence: PMID:24739963 Izumo1 is an essential sperm cell-surface protein, but its receptor on the egg has not been described. PMID:15759005 Human sperm also contain Izumo and addition of the antibody against human Izumo left the sperm unable to fuse with zona-free hamster eggs. |
| GO:0007155 cell adhesion | IC PMID:15759005 The immunoglobulin superfamily protein Izumo is required for... | MODIFY | Summary: Inferred from the role of IZUMO1 in sperm-egg membrane interaction. Reason: Correct but very general. IZUMO1 mediates adhesion between two different cell types (sperm and egg) through JUNO binding; the heterotypic cell-cell adhesion term, already carried by the gene, is the appropriately specific adhesion process. Proposed replacements: heterotypic cell-cell adhesion Supporting Evidence: PMID:36070373 Fertilizing sperm display oscillatory motility tethered to the oolemma due to the initial JUNO/IZUMO1 interaction. |
| GO:0007165 signal transduction | IEA GO_REF:0000108 | REMOVE | Summary: Inter-ontology inference from receptor ligand activity. Reason: This IEA follows only from the receptor ligand activity mapping. No signaling cascade downstream of IZUMO1-JUNO binding has been shown; the interaction is an adhesion event. There is no independent evidence that IZUMO1 takes part in signal transduction. Supporting Evidence: file:human/IZUMO1/IZUMO1-uniprot.txt The IZUMO1:IZUMO1R/JUNO interaction is a necessary adhesion event between sperm and egg that is required for fertilization but is not sufficient for cell fusion. |
| GO:0007339 binding of sperm to zona pellucida | IBA GO_REF:0000033 | REMOVE | Summary: Propagated assertion that IZUMO1 mediates sperm binding to the zona pellucida. Reason: Contradicted by the knockout phenotype. Izumo1-null sperm bind to and penetrate the zona pellucida normally and fail only at fusion with the egg plasma membrane. IZUMO1 is not exposed until the acrosome reaction and binds oolemmal JUNO, not zona proteins. Recognition of the egg plasma membrane is captured by sperm-egg recognition. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN008053906 UNRESOLVED Ancestral Izumo-family node carrying zona-binding; contradicted for IZUMO1 by the mouse knockout in which null sperm bind and penetrate the zona normally. RGD:1565454 UNRESOLVED Rat Izumo1 descendant evidence not inspected; may reflect a sperm-binding assay not resolving zona versus oolemma. Supporting Evidence: PMID:15759005 They produced normal-looking sperm that bound to and penetrated the zona pellucida but were incapable of fusing with eggs. |
| GO:0007339 binding of sperm to zona pellucida | IEA GO_REF:0000107 | REMOVE | Summary: Propagated assertion that IZUMO1 mediates sperm binding to the zona pellucida. Reason: Contradicted by the knockout phenotype. Izumo1-null sperm bind to and penetrate the zona pellucida normally and fail only at fusion with the egg plasma membrane. IZUMO1 is not exposed until the acrosome reaction and binds oolemmal JUNO, not zona proteins. Recognition of the egg plasma membrane is captured by sperm-egg recognition. Supporting Evidence: PMID:15759005 They produced normal-looking sperm that bound to and penetrated the zona pellucida but were incapable of fusing with eggs. |
| GO:0007342 fusion of sperm to egg plasma membrane involved in single fertilization | IBA GO_REF:0000033 | ACCEPT | Summary: IZUMO1 is essential for sperm fusion with the egg plasma membrane. Reason: Knockout mice and blocking antibodies against human IZUMO1 abolish fusion of sperm with the egg. IZUMO1 contributes the gamete-adhesion step of the fusion process (JUNO and FCRL3/MAIA binding) and is the core process for this gene, although it is probably not itself the fusogen. Supporting Evidence: PMID:15759005 Human sperm also contain Izumo and addition of the antibody against human Izumo left the sperm unable to fuse with zona-free hamster eggs. PMID:36070373 MAIA forms a highly stable interaction with the known IZUMO1/JUNO sperm-egg complex, permitting specific gamete fusion. |
| GO:0007342 fusion of sperm to egg plasma membrane involved in single fertilization | IDA PMID:15759005 The immunoglobulin superfamily protein Izumo is required for... | ACCEPT | Summary: IZUMO1 is essential for sperm fusion with the egg plasma membrane. Reason: Knockout mice and blocking antibodies against human IZUMO1 abolish fusion of sperm with the egg. IZUMO1 contributes the gamete-adhesion step of the fusion process (JUNO and FCRL3/MAIA binding) and is the core process for this gene, although it is probably not itself the fusogen. Supporting Evidence: PMID:15759005 Human sperm also contain Izumo and addition of the antibody against human Izumo left the sperm unable to fuse with zona-free hamster eggs. PMID:36070373 MAIA forms a highly stable interaction with the known IZUMO1/JUNO sperm-egg complex, permitting specific gamete fusion. |
| GO:0007342 fusion of sperm to egg plasma membrane involved in single fertilization | IEA GO_REF:0000002 | ACCEPT | Summary: IZUMO1 is essential for sperm fusion with the egg plasma membrane. Reason: Knockout mice and blocking antibodies against human IZUMO1 abolish fusion of sperm with the egg. IZUMO1 contributes the gamete-adhesion step of the fusion process (JUNO and FCRL3/MAIA binding) and is the core process for this gene, although it is probably not itself the fusogen. Supporting Evidence: PMID:15759005 Human sperm also contain Izumo and addition of the antibody against human Izumo left the sperm unable to fuse with zona-free hamster eggs. PMID:36070373 MAIA forms a highly stable interaction with the known IZUMO1/JUNO sperm-egg complex, permitting specific gamete fusion. |
| GO:0007342 fusion of sperm to egg plasma membrane involved in single fertilization | NAS PMID:24739963 Juno is the egg Izumo receptor and is essential for mammalia... | ACCEPT | Summary: IZUMO1 is essential for sperm fusion with the egg plasma membrane. Reason: Knockout mice and blocking antibodies against human IZUMO1 abolish fusion of sperm with the egg. IZUMO1 contributes the gamete-adhesion step of the fusion process (JUNO and FCRL3/MAIA binding) and is the core process for this gene, although it is probably not itself the fusogen. Supporting Evidence: PMID:15759005 Human sperm also contain Izumo and addition of the antibody against human Izumo left the sperm unable to fuse with zona-free hamster eggs. PMID:36070373 MAIA forms a highly stable interaction with the known IZUMO1/JUNO sperm-egg complex, permitting specific gamete fusion. |
| GO:0016020 membrane | IDA PMID:15759005 The immunoglobulin superfamily protein Izumo is required for... | MODIFY | Summary: IZUMO1 is a single-pass membrane protein. Reason: The membrane is correct but too general; the evidence places IZUMO1 at the sperm plasma membrane after the acrosome reaction (and acrosomal membrane before it). Plasma membrane is already carried by the gene. Proposed replacements: plasma membrane Supporting Evidence: PMID:24739963 Izumo1 is an essential sperm cell-surface protein, but its receptor on the egg has not been described. |
| GO:0016020 membrane | IEA GO_REF:0000120 | MODIFY | Summary: IZUMO1 is a single-pass membrane protein. Reason: The membrane is correct but too general; the evidence places IZUMO1 at the sperm plasma membrane after the acrosome reaction (and acrosomal membrane before it). Plasma membrane is already carried by the gene. Proposed replacements: plasma membrane Supporting Evidence: PMID:24739963 Izumo1 is an essential sperm cell-surface protein, but its receptor on the egg has not been described. |
| GO:0034113 heterotypic cell-cell adhesion | IEA GO_REF:0000108 | ACCEPT | Summary: IZUMO1 mediates adhesion of sperm to the egg plasma membrane. Reason: Binding of sperm IZUMO1 to egg JUNO tethers the two gametes, a heterotypic cell-cell adhesion event. Supporting Evidence: PMID:36070373 Fertilizing sperm display oscillatory motility tethered to the oolemma due to the initial JUNO/IZUMO1 interaction. |
| GO:0035036 sperm-egg recognition | IDA PMID:39423812 A conserved fertilization complex bridges sperm and egg in v... | ACCEPT | Summary: IZUMO1 mediates recognition of the egg plasma membrane through JUNO. Reason: IZUMO1-JUNO is the receptor pair for sperm-oolemma recognition; the human IZUMO1-SPACA6-TMEM81 complex interacts in vitro and forms the conserved sperm-side recognition complex. Supporting Evidence: PMID:24739963 We show that the Izumo1-Juno interaction is conserved within several mammalian species, including humans. PMID:39423812 a conserved sperm complex binds to divergent egg proteins-Bouncer in fish and JUNO in mammals-to mediate sperm-egg interaction |
| GO:0035036 sperm-egg recognition | IEA GO_REF:0000002 | ACCEPT | Summary: IZUMO1 mediates recognition of the egg plasma membrane through JUNO. Reason: IZUMO1-JUNO is the receptor pair for sperm-oolemma recognition; the human IZUMO1-SPACA6-TMEM81 complex interacts in vitro and forms the conserved sperm-side recognition complex. Supporting Evidence: PMID:24739963 We show that the Izumo1-Juno interaction is conserved within several mammalian species, including humans. PMID:39423812 a conserved sperm complex binds to divergent egg proteins-Bouncer in fish and JUNO in mammals-to mediate sperm-egg interaction |
| GO:0035036 sperm-egg recognition | ISS GO_REF:0000024 | ACCEPT | Summary: IZUMO1 mediates recognition of the egg plasma membrane through JUNO. Reason: IZUMO1-JUNO is the receptor pair for sperm-oolemma recognition; the human IZUMO1-SPACA6-TMEM81 complex interacts in vitro and forms the conserved sperm-side recognition complex. Supporting Evidence: PMID:24739963 We show that the Izumo1-Juno interaction is conserved within several mammalian species, including humans. PMID:39423812 a conserved sperm complex binds to divergent egg proteins-Bouncer in fish and JUNO in mammals-to mediate sperm-egg interaction |
| GO:0042803 protein homodimerization activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IZUMO1 can form disulfide-linked homodimers and oligomers. Reason: Context-dependent homodimerization is reported (JUNO binding induces dimerization in mouse), but it is a structural feature of the adhesion mechanism, not the core activity. Supporting Evidence: file:human/IZUMO1/IZUMO1-uniprot.txt Monomer, homodimer; disulfide-linked and homooligomer; depending on the context |
| GO:0042803 protein homodimerization activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: IZUMO1 can form disulfide-linked homodimers and oligomers. Reason: Context-dependent homodimerization is reported (JUNO binding induces dimerization in mouse), but it is a structural feature of the adhesion mechanism, not the core activity. Supporting Evidence: file:human/IZUMO1/IZUMO1-uniprot.txt Monomer, homodimer; disulfide-linked and homooligomer; depending on the context |
| GO:0048018 receptor ligand activity | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IZUMO1 is often described as the ligand of the JUNO receptor. Reason: IZUMO1 does bind JUNO, but receptor ligand activity (a signaling receptor activator) asserts that binding changes the activity of the receptor. JUNO is a GPI-anchored protein with no known signaling function, and the interaction is a gamete adhesion event. Its binding activity is better captured by protein binding involved in heterotypic cell-cell adhesion. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN008053906 SUPPORTS SOURCE BUT NOT TARGET Node correctly captures JUNO binding but frames it as signaling-receptor ligand activity; the conserved activity is gamete adhesion. MGI:MGI:1920706 SUPPORTS SOURCE BUT NOT TARGET Mouse Izumo1 binds Juno; no evidence that binding changes receptor activity. Supporting Evidence: file:human/IZUMO1/IZUMO1-uniprot.txt The ligand-receptor interaction probably does not act as a membrane 'fusogen'. PMID:24739963 We show that the Izumo1-Juno interaction is conserved within several mammalian species, including humans. |
| GO:0048018 receptor ligand activity | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: IZUMO1 is often described as the ligand of the JUNO receptor. Reason: IZUMO1 does bind JUNO, but receptor ligand activity (a signaling receptor activator) asserts that binding changes the activity of the receptor. JUNO is a GPI-anchored protein with no known signaling function, and the interaction is a gamete adhesion event. Its binding activity is better captured by protein binding involved in heterotypic cell-cell adhesion. Supporting Evidence: file:human/IZUMO1/IZUMO1-uniprot.txt The ligand-receptor interaction probably does not act as a membrane 'fusogen'. PMID:24739963 We show that the Izumo1-Juno interaction is conserved within several mammalian species, including humans. |
| GO:0086080 protein binding involved in heterotypic cell-cell adhesion | IBA GO_REF:0000033 | ACCEPT | Summary: IZUMO1 binds egg JUNO (and, in humans, FCRL3/MAIA) to adhere sperm to the egg. Reason: This is the core molecular activity of IZUMO1, supported by binding, structural and genetic data, including for the human proteins. Supporting Evidence: PMID:27309808 The central Ξ²-hairpin region of IZUMO1 provides the main platform for JUNO binding PMID:36070373 MAIA forms a highly stable interaction with the known IZUMO1/JUNO sperm-egg complex, permitting specific gamete fusion. |
| GO:0086080 protein binding involved in heterotypic cell-cell adhesion | ISS GO_REF:0000024 | ACCEPT | Summary: IZUMO1 binds egg JUNO (and, in humans, FCRL3/MAIA) to adhere sperm to the egg. Reason: This is the core molecular activity of IZUMO1, supported by binding, structural and genetic data, including for the human proteins. Supporting Evidence: PMID:27309808 The central Ξ²-hairpin region of IZUMO1 provides the main platform for JUNO binding PMID:36070373 MAIA forms a highly stable interaction with the known IZUMO1/JUNO sperm-egg complex, permitting specific gamete fusion. |
| GO:0098635 protein complex involved in cell-cell adhesion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: IZUMO1 is part of a multimeric sperm complex (with SPACA6 and TMEM81) that mediates binding to the egg. Reason: The human orthologs of the IZUMO1-SPACA6-TMEM81 trimer interact in vitro, and the complex engages the egg receptor, consistent with a cell-cell adhesion complex. Its composition and stoichiometry in human sperm are still being defined. Supporting Evidence: PMID:39423812 we show that Izumo1, Spaca6, and Tmem81 interact in zebrafish sperm and that the human orthologs interact in vitro |
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Download this section (compressed HTML)Q: Is IZUMO1 itself part of the fusion machinery, or does it only provide adhesion while another sperm or egg protein acts as the fusogen?
Q: How do JUNO and FCRL3/MAIA binding events coordinate in time on the human oolemma?
Experiment: Reconstitute human IZUMO1-SPACA6-TMEM81 complexes on cells or proteoliposomes and measure binding to JUNO and FCRL3/MAIA and any induced membrane fusion.
Type: biochemical reconstitution
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